The preparation of immediate-release and sustained-release dosage forms is well known. One major problem has been the preparation of a single dosage form wherein one medicament is to be provided for immediate-release and another medicament, or more of the same medicament, is provided for sustained-release over a longer, specific period of time.
U.S. Pat. Nos. 4,226,848 and 4,250,163 to Nagai et al. disclose a method for the controlled administration a medicament to the mucosa of the nasal cavity or the oral cavity by adhering the medicament with a polymeric matrix comprising about 50% to about 95% cellulose ether, such as methyl cellulose, hydroxypropylmethyl cellulose and the like, and about 50% to about 5% homopolymer or copolymer of acrylic acid. The medicament may be analgesic and anti-inflammatory agents, antihistamines, antibiotics, antibacterial agents, chemotherapeutic agents, local anesthesics, cardiac agents, vasodilators, antitussives and expectorants, oral antiseptics, enzyme proteins, hypoglycemic agents, hemostats, hormones, hypotensive agents, sedatives or tranquilizers, antitumor agents, gastro-intestinal drugs and antacids. The medicament is uniformly dispersed into the polymeric matrix and formed, by conventional means, into tablets, granules, powders and the like. The adherence of the preparation to the particular muscosal area allows a high concentration of medicament to be applied locally to a diseased area or to an optimal site of absorption.
European Patent No. A-0111144 to Merrell Dow Pharmaceuticals, Inc. teaches a sustained-release, solid dosage form having a core and one or more concentric enveloping sustained-release layers wherein the concentration of the medicament is greatest in the core and diminishes in each subsequent outer layer which allows zero-order release of the medicament. This disclosure provides further teaching in that the outer layer is a quickly-dissolving nonsustained-release layer which allows rapid onset of medicament effect and the underlying layers provide sustained-release medicaments, as does the core. The matrix is a hydrophilic gel such as hydroxypropyl methylcellulose or mixtures of such gels to effect particular release rates.
U.S. Pat. No. 4,260,596 to Mackles describes an edible unit dosage form having a hard outer shell comprising about 80% to about 100% mannitol which encloses a soft or liquid inner medicament-containing center. The outer shell is sealed by use of a sealing mixture which is poured into an opening in the shell, then allowed to cool and harden. Typical medicaments include topical antiseptics, topical anesthetics, analgesics and antipyretics, cough suppressants, antihistamines, pulmonary decongestants, antacids and the like and mixtures thereof.
U.S. Pat. No. 4,427,681 to Munski teaches a thixotropic gel composition containing a mixture of microcrystalline cellulose, sodium carboxymethylcellulose as the suspending agent and titanium dioxide as an opacifying agent which is easily convertible by moderate hand shaking into a pourable liquid. Typical compositions include cough syrups and sore throat and cough suppressant medication formulations. Typical medicaments may include combinations of pseudoephedrine and salicylates.
U.S. Pat. No. 4,449,983 to Cortese et al. describes an osmotic device in which the medicament compartments are separated by a hydrogel (swellable, hydrophilic polymer) such as cross-linked poly(hydroxyalkyl methacrylate) and poly(-vinyl alcohol) material. The outer wall of the device is formed from osmosis and reverse osmosis polymers such as cellulose acylate, cellulose acetate, beta-glycan acetate, polyurethane, cellulose acetate succinate, and the like. Medicament combinations can include decongestants and analgesics.
U.S. Pat. Nos. 4,601,894 and 4,657,757 to Hanna et al. disclose controlled-release matrix dosage forms containing acetaminophen, pseudoephedrine sulfate and dextrobrompheniramine maleate in a single homogeneous mixture of hydroxypropyl methylcellulose and ethers and other cellulose and cellulose ether derivatives which provide release of each active at its desired rate over a period of 2-14 hours.
U.S. Pat. No. 4,678,516 to Alderman et al. teaches a thermoformable sustained-release matrix comprised of hydroxypropyl methylcellulose and a major amount (at least about 30% by weight) of a plasticizer such as polyethylene glycol. Typical medicaments include herbicides, insecticides, nematocides, fungicides, antimicrobials, medicaments, vitamins, coloring agents and preservatives.
U.S. Pat. No. 4,695,591 to Hanna et al. is directed to a controlled-release dosage form incorporating an analgesic-effective amount of acetaminophen, an antihistaminic-effective amount of dexbrompheniramine maleate, a decongestant-effective amount of pseudoephedrine sulfate and 4.6% to 12% hydroxypropyl methycellulose U.S.P. 2910 as the carrier base. This dosage form is prepared by (1) blending all of the ingredients together, (2) granulating the powder blend, (3) drying the granules and milling if necessary, (4) blending the granules with lubricants, and (5) compressing and then coating the compressed tablets, if desired.
U.S. Pat. No. 4,789,549 to Khan et al. discloses a sustained-release dosage form wherein the tendency for an initial surge of medicament in the first hour is prevented, comprising coating a medicament in a water soluble polymer matrix with a semipermeable membrane consisting of hydroxypropyl cellulose and cellulose acetate phthalate with polyoxpropylene polyoxethylene block copolymer and acetylated monoglycerides. The ratio of medicament to water soluble polymer matrix can vary from about 90%:10% to about 78%:22%. The preferred medicament is diphenhydramine hydrochloride or disopyramide phosphate.
Applicant has unexpectedly found a solution to the two medicament delivery system problem by providing a tablet comprising at least two layers wherein the first layer is readily disintegratable and provides immediate-release of the medicament and the second layer displays increased resistance to disintegration and erosion relative to the first layer and thereby provides sustained-release of the medicament. Applicant's inventive tablet also provides the advantage of being a directly compressible layered tablet.